Infectious Diseases in Pediatrics

Fever

General considerations

Fever is the most common reason for pediatric consultations and emergency visits. Several definitions of fever exist, but most experts define fever as a rectal temperature of

38°C or above. Temperature in pediatric patients can be measured in a variety of manners:

‒ rectal (using a mercury or digital thermometer). ‒ oral (mercury or digital).‒ axillary (mercury, digital, or liquid crystal strip).‒ forehead (liquid crystal strip).‒ tympanic (using a device that measures thermal infrared energy from the tympanic

membrane).

Causes Fever occurs when there is a rise in the hypothalamic set-point in response to endogenously

produced pyrogens. Causes of fever include infections, malignancies, autoimmune diseases, metabolic diseases,

chronic inflammatory conditions, medications (including immunizations), central nervous system abnormalities, and exposure to excessive environmental heat. The majority of fevers in pediatric patients are caused by self-limiting viral infections. Fever may be due to (1) simple focal infections e.g. tonsillitis, (2) serious focal infections e.g. meningitis or pneumonia, or (3) fever without focus i.e. due to viremia, bacteremia or septicemia.

Common causes of acute fevero Upper Respiratory Tract Disease

Such as viral respiratory tract disease, Otitis media, sinusitiso Lower Respiratory Tract Disease

Such as bronchiolitis, pneumoniao Gastrointestinal Disorders

Such asbBacterial gastroenteritis, viral gastroenteritiso Exanthems

Examples include measles, rubella, roseola infantum, varicella and scarlet fever. All viral rashes need symptomatic treatment and antipyretics. Scarlet fever (streptococcal infection) is treated by oral penicillin.o Musculoskeletal Infections

o Others: urinary Tract Infections , bacteremia, meningitis

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Initial Evaluation When evaluating a child with fever, one should elicit from the parents information about:

‒ the duration of fever, and how the temperature was taken. ‒ the maximum height of fever documented at home, all associated symptoms, any chronic

medical conditions, any medications taken, medication allergies, fluid intake, urine output, exposures and travel, and any additional features of the illness that concern the parents.

‒ temperature, heart rate, respiratory rate, and blood pressure should be documented, as well as an oxygen saturation if the child has any increased work of breathing.

‒ a complete physical examination, including neurologic examination, should be performed, with particular attention paid to the child's degree of toxicity and hydration status.

A well-appearing, well-hydrated child with evidence of a routine viral infection can be safely sent home with symptomatic treatment and careful return precautions.

Treatment Fever phobia is a term that describes parents' anxious response to the fevers that all children

experience; most of caregivers thought that a fever could cause harmful effects. Parents need to be reassured that fevers lower than 41.7°C do not cause brain damage. They should be counseled that, although fevers can occasionally cause seizures, febrile seizures are generally harmless and likewise do not cause brain damage.

Several safe and effective medications are available for the treatment of fever. Antipyretics lower the central set point in CNS, inhibit cyclo-oxygenase enzyme, and prevent

synthesis of prostaglandin ‒ Acetaminophen is indicated in children who have fever of 39°C or are uncomfortable.

Acetaminophen is given in a dosage of 10-15 mg/kg of body weight per dose and can be given every 4–6 hours.

‒ Ibuprofen is given in a dosage of 10 mg/kg of body weight per dose and can be given every 6–8 hours. Ibuprofen and acetaminophen are similar in safety and their ability to reduce fever; however, ibuprofen is longer lasting.

‒ Aspirin should not be used for treating fever in any child or adolescent, because of its association with the development of Reye syndrome (particularly during infections with varicella and influenza).

Antipyretics – guidelines

Antipyretics do not prevent febrile convulsions and should not be used specifically for this purpose.

Do not routinely give antipyretic drugs to a child with fever with the sole aim of reducing body temperature.

Do not administer paracetamol and ibuprofen at the same time but consider using the alternative agent if the child does not respond to the first drug.

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Adjunctive measures for treating fever include:o Adequate hydration

o Comfortable surroundings: temperature (22o C)

o Not bundled in extra clothing or blankets

o Sponging with tepid water (temperature around 27o C)

o ice baths or alcohol should be avoided: lead to shivering which may increase body

temperature and is uncomfortable

Common Upper Respiratory Tract Infections

Acute Nasopharyngitis (Coryza)– The commonest infection in childhood, mostly due to viral agents e.g. rhinoviruses.– Clinical features include low grade fever, nasal discharge and nasal block.– Complications are spread of infection and possible precipitation of asthmatic attack.– Uncomplicated cases are treated by antipyretics and decongestants without antibiotics.

Acute Otitis Media (AOM)– A suppurative infection of the middle ear cavity which arises as a complication of

preceding viral respiratory infection.– Common bacterial pathogens achieve access through blocked eustachian tube

(infection, pharyngitis, or hypertrophied adenoids).– Common bacterial pathogens are S. pnuemoniae, H. influenza, and M. catarrhalis. – Symptoms may include:

– Fever -- Irritability– Poor feeding -- Otalgia – Otorrhea -- Signs of a common cold

– Otoscopy is the standard for clinical diagnosis.– Treatment Recommendations

– Infants younger than 6 months should receive antibiotics.– Children 6 months to 2 years should receive antibiotics if the diagnosis is

certain. If diagnosis is uncertain; observation period 48 to 72 hours with analgesics and follow up.

– Children 2 years and older should receive antibiotics if diagnosis is certain or illness severe. Observation period is an option.

– Treatment– Amoxicillin – First line therapy– Second line therapy

– Amoxicillin-clavulanate– Cefuroxime axetil – Cefdinir– Ceftriaxone

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Acute Pharyngitis/Acute Tonsillitis‒ Caused by many infectious agents. Most common bacterial agents are group A

streptococci (Strep pyogenes). Most common viral are rhinovirus, adenovirus, influenza, coxsackievirus, echovirus, and Epstein Barr virus.

‒ Clinical Manifestations include sore throat, dysphagia, and abdominal pain. Examination reveals red pharynx and enlarged tonsils with a yellow exudates. Cervical lymph nodes are tender and enlarged.

‒ Diagnosis: The challenge is to distinguish pharyngitis caused by group A streptococci from pharyngitis caused by nonstreptococcal organisms. Throat culture is the diagnostic

“gold standard”. Rapid streptococcal antigen tests are available and helpful. Bacterial

pharyngitis is relatively uncommon before 2 to 3 years of age with increased incidence school-age children.

‒ Treatment: Streptococcal infection is treated by antimicrobial therapy which accelerates clinical recovery by 12-24 hours. Oral penicillin is given orally three or four times daily for a full 10 days. Major benefit of antimicrobial therapy is the prevention of acute rheumatic fever.

Acute Sinusitis‒ Sinusitis is inflammation of the paranasal sinuses which can be viral, allergic, or bacterial

in origin. Persistent upper respiratory tract symptoms (nasal congestion, rhinorrhea, and cough) are the most common complaint in the pediatric office.

‒ Sinus Developmento Maxillary and ethmoid sinuses – present at birth

o Frontal Sinuses and sphenoid sinuses develop by the 5th or 6th birthday

‒ Causes include Streptococcus pneumoniae (30-40%), Haemophilus influenzae (20%), Moraxella catarrhalis (20%), and Viruses (10%).

‒ Medical Treatment: ‒ First Line:

o Amoxicillin 80-90 mg/kg/day for 10-14 days

o Longer treatments may be considered in chronic sinusitis or to avoid surgery

‒ Alternatives:o Amoxicillin-clavulanate, cefuroxime axetil, cefpodoxime, macrolides

o Consider an alternative if amoxicillin allergy, recent treatment with amoxicillin,

or failure of clinical improvement on amoxicillin within 72 hours‒ Adjuvant therapies: Antihistamines, decongestants, anti-inflammatory and Nasal

irrigation with saline.

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‒ Patients with chronic or recurrent sinusitis, who fail to improve with maximal medical therapy, may consider sinus surgery.

Acute Gastroenteritis (Acute Diarrhea)Gastroenteritis (GE) is a common illness in infants and young children. It usually causes diarrhea (watery or frequent motions) and vomiting. Viruses account for approximately 70% of episodes of acute infectious diarrhea in children, with rotavirus being the most common cause. Rotavirus infection is associated with approximately half of acute GE hospitalizations in children, peaking in the 6–24 months age group.

Bacteria account for approximately 15% of episodes; bacterial GE is generally more common in the first few months of life, and then in the school aged child. The most common bacterial causes are salmonella spp., Campylobacter jejuni, Escherichia coli, and shigella spp. Giardia lamblia is the most common protozoal cause of GE, but tends to be associated with more persistent diarrhoea. Other protozoa include cryptosporidium spp. and Entamoeba histolytica.Even though the number of death associated to AGE worldwide is still high, a decrease has been noticed since the start of Oral Rehydration Therapy (ORT) campaigns.

Clinical featuresChildren with viral GE typically present with watery diarrhea without the presence of blood, with or without vomiting, low grade fever and anorexia. Most are less than 5 years of age. The typical peak period is in the autumn or winter months. A history of contact with GE may be present. Bacterial GE may be associated with food or water borne infections. It is usually characterized by the presence of bloody diarrhea, mucous in the stools and a high fever.

Assessment of dehydrationThe most important complication of GE is dehydration. The risk of dehydration is increased with younger age. The amount of weight loss as a percentage of normal body weight provides the best estimate of degree of dehydration; however, it is not always practical to calculate this. Clinical signs are not present until the child has lost at least 4% of their bodyweight.The best signs for identifying dehydration include:

‒ Dry, sticky mouth‒ Few or no tears when crying‒ Sunken eyes, dry and cool skin‒ Lack urine or wet diaper

Complications of Diarrhea• Dehydration and electrolyte disturbances• Metabolic Acidosis (reduced pH and serum bicarbonate)• Gastrointestinal complications

o Secondary carbohydrate malabsorption

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o Protein intolerance

o Persistent diarrhea

• Nutritional complications (malnutrition and weight loss)

ManagementMost infants and children can be rehydrated safely with oral rehydration solution (ORS). This may be given orally or if this is unsuccessful, via nasogastric administration. The use of ORS is based on the principle of glucose facilitated sodium transport in the small intestine. Breastfed children should continue to breastfeed through the rehydration and maintenance phases of their acute GE. Additional ORS can be given if required. In the dehydrated child who is normally fed with formula, formula feeds should stop during rehydration and restart as soon as the child is rehydrated. Dilution of formula is unnecessary when formula is reintroduced.

Emergency Department Management• Mild to Moderate Dehydration: Administer 50-100 ml of ORS/kg during 2-4 hr. Additional

ORS should be administered for ongoing losses.• Severe Dehydration: Constitutes a medical emergency and requires immediate IV

rehydration. 20 ml/kg of Lactated Ringers or Normal Saline should be administered until pulse, perfusion and mental status returns to normal. As soon as the signs of severe dehydration have resolved the patient may be started on ORT.

ORS Therapy includes two phases:• Rehydration Phase: Water and electrolytes are provided via (ORS) replacing existing losses. • Maintenance Phase: Replacement of ongoing fluid and electrolyte losses and adequate dietary intake. Studies have shown that an early return to feeding shortens the duration of diarrhea and improves weight gain without increasing vomiting or diarrhea.

Choices of ORS

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- New multiple controlled trials have supported the adoption of a lower osmolarity solution. Lower osmolarity has been associated to less stool output, less vomiting and reduced need of intravenous therapy among infants and children.

Types of ORS:

SolutionGlu

g/dl

Na

mEq/L

K

meq/L

Cl

meq/LWHO 2.0 90 20 80

Rehydralyte 2.5 75 20 65

Pedialyte 2.5 45 20 35

Infalyte 2.0 50 20 40

Advantages of Oral Rehydration Solution (ORS):• Effective in all types & all degrees of dehydration.• Can prevent dehydration if given early in the disease.• Cheap, easy to administer; can be given by mother at home (Lower hospitalization rate). • No chance of over hydration or electrolyte overdose.

Dietary Therapy Withholding food for 24 hr is unnecessary. Once rehydration is achieved patient should continue with their age-appropriate diets. Lactose-free or lactose-reduced formulas are not necessary, except in children with severe malnutrition. Clinical trials have indicated that the use of diluted formulas is associated with prolongation of symptoms and delayed nutritional recovery. Soy formulas have been marketed to reduce diarrhea, but the added soy reduce the liquid stools without changing the actual output volume. Children receiving a solid or semisolid diet should continue their usual diet. Avoid foods with high simple sugars, which may cause osmotic diarrhea.

Pharmacologic Therapy- Antibiotics or antiviral medications are not prescribed for cases of diarrhea caused by virus or bacteria. Antibiotics may be given to very young children or children with weak immune system.- In parasitic infection – antiparasitic medicine is usually given e.g. metronidazole for giardiasis.- Antiemetics and antidiarrheals are not generally indicated in children with acute gastroenteritis- Probiotics are live microorganisms in fermented foods that promote improved balance in

intestinal microflora. Most common species studied included Lactobacilli. Mechanism of action

include, enhancing host defenses, competition of pathogenic flora for receptor sites and production of antibiotic substances.

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- Prebiotics are complex carbohydrates that stimulate the growth of health promoting intestinal flora. The oligosaccharides contained in breast milk are the prototypic prebiotic. Data have associated the oligosaccharides in breast milk to the lowered incidence of acute diarrhea in the breast feed infant.

Childhood Tuberculosis

- About one million children develop tuberculosis (TB) annually worldwide, accounting for about 11% of all TB cases. Children with TB differ from adults in their immunological and pathophysiological response in ways that may have important implications for the prevention, diagnosis and treatment of TB in children.- Infection with M. tuberculosis usually results from inhalation into the lungs of infected droplets produced by someone who is coughing and who has pulmonary TB disease. The source of infection of most children is an infectious adult in their close environment (usually the household). This exposure leads to the development of a primary parenchymal lesion (Ghon focus) in the lung with spread to the regional lymph node(s). In the majority of cases, the resultant cell-mediated immunity contains the disease process at this stage. Risk of disease progression is increased in the very young (< 3 years old) and in immune compromised children.

Diagnosis of tuberculosis in children

Most children with TB have pulmonary TB. In most immunocompetent children, TB presents with symptoms of a chronic disease after they have been in contact with an infectious source. Infection with M. tuberculosis can be demonstrated by a TST, and CXR changes typical of TB are usually present. The presentation in infants may be more acute, resembling acute severe pneumonia, and should be suspected when there is poor response to antibiotics.

The presence of three or more of the following should strongly suggest the diagnosis of TB1) Chronic symptoms suggestive of TB e.g. chronic, cough, fever and weight loss2) Physical signs highly of suggestive of TB e.g. persistent pneumonia3) A positive tuberculin skin test4) Chest radiograph suggestive of TB

After TB is diagnosed in a child or adolescent, an effort should be made to detect the adult source cases, and especially other undiagnosed household cases.- Tuberculin skin test: A positive tuberculin skin test (TST) occurs when a child is infected with M. tuberculosis. However, in children, TST can also be used as an adjunct in diagnosing TB disease, when it is used in conjunction with signs and symptoms of TB and other diagnostic tests. There are a number of TSTs available, but the Mantoux skin test is the recommended test.- Bacteriological confirmation: It is always preferable to make a bacteriological diagnosis of TB in a child using whatever specimens and laboratory methods are available. Samples include sputum, gastric aspirate and other material (e.g., lymph node biopsy or any other material that is biopsied).

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- Chest x-ray: In the majority of cases, children with pulmonary TB have CXR changes suggestive of TB. The commonest picture is that of persistent opacification in the lung together with enlarged hilar lymph glands. A miliary pattern of opacification is highly suggestive of TB.

Treatment of tuberculosis in children TB chemotherapy should be based on two important microbiological considerations:

1. The combination of drugs to avoid the development of resistance.2. The need for prolonged chemotherapy to prevent disease relapse.

Phases of treatmentThe intensive phase

• usually covers the first 2 months of treatment. • During this phase, most of the bacilli will be killed. • The sputum converts from positive to negative in more than 80 % of the new patients

within the first 2 months of treatment. The continuation phase

• usually lasts 4-6 months, depending on the treatment regimen. • This phase is intended to eliminate the remaining dormant bacilli. • These dormant bacilli decrease constantly as treatment intake progresses.

Antituberculosis drugs- First-line oral agents

o Isoniazid (H) – backbone of TB chemotherapy and treatment. Bactericidal.

o Rifampicin (R) – bactericidal and a key sterilizing drug in short-course treatment.

o Pyrazinamide (Z) – high sterilizing activity. Kill slow growing tubercle bacilli in acidic

pH inside macrophages.o Ethambutol (E) – bacteriostatic at low doses (15 mg/kg/day), bactericidal at higher doses

25 mg/kg/day. The primary role is to prevent the emergence of drug resistance to companion drugs.

- Special considerations Studies of ethambutol, pyrazinamide and isoniazid have found lower plasma drug levels

in children than adults, using the same dosages. Young children have greater extra-vascular fluid volume and greater liver mass

proportionally to body mass. Malnourished children have higher rates of hepatotoxicity. Children with more advanced forms of disease may experience more significant

hepatotoxic reactions than less severe children.- Drug doses for childrenDrug Daily dose and range

(mg/kg body weight)Daily maximum (mg)

Isoniazid 10 (10-15) 300

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Rifampicin 15 (10-20) 600

Pyrazinamide 35 (30-40) 2000

Standards for Pediatric Immunization Practices

Compliance with the manufacturer's recommendations for route and site of administration of injectable vaccines are critical for safety and efficacy. ‒ All vaccines containing an adjuvant must be administered intramuscularly to avoid

granuloma formation or necrosis. With the exception of Bacillus Calmette-Guérin (BCG) vaccine, all vaccines are given either intramuscularly or subcutaneously.

‒ Intramuscular injections are given at a 90-degree angle to the skin, using a needle that is sufficiently long to reach the muscle tissue, but not so long as to injure underlying nerves, blood vessels, or bones. The anterolateral thigh is the preferred site of vaccination in newborns and children up to 2 years of age, and the deltoid muscle of the arm is the preferred site for children aged 3–18 years.

‒ Subcutaneous injections should be administered at a 45-degree angle into the anterolateral aspect of the thigh (for infants younger than 12 months) or the upper outer triceps area (for children 12 months and older).

Many combinations of vaccines can be administered simultaneously without increasing the risk of adverse effects or compromising immune response. Inactivated vaccines can be given simultaneously with, or at any time after, a different vaccine. Injectable or nasally given live-virus vaccines, if not administered on the same day, should be given at least 4 weeks apart (eg, measles-mumps-rubella [MMR] and varicella [VAR]).

Lapses in the immunization schedule do not call for reinstitution of the series. Extra doses of hepatitis B (HepB), Hib, MMR, and VAR are not harmful, but repetitive exposure to tetanus vaccine beyond the recommended intervals can result in hypersensitivity reactions and should be avoided.

If an immunoglobulin (Ig) or blood product has been administered, live-virus vaccination should be delayed 3–11 months, depending on the product, to avoid interference with the immune response.

Longer than recommended intervals between vaccinations does not reduce final antibody titers, and lapsed schedules do not require restarting the series.

Vaccines very rarely cause acute anaphylactic-type reactions. Nonetheless, all vaccine providers should have the equipment, medications, staff, and training to manage emergencies that may occur following vaccination.

Routine Childhood Immunizations

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Combination vaccines help solve the problem of large numbers of injections during any single clinic visit. Currently available combination vaccines include MMR, measles-mumps-rubella-varicella (MMRV), and various combinations of Hib, HepB, IPV, and DTaP, including DTaP-HepB-IPV and DTaP-IPV-Hib combination vaccines.

Egyptian Schedule for Infant Immunization

Age Vaccines

At birth OPV (zero) BCG

At 2 months of age OPV (1) DPT (1) HB (1)

At 4 months of age OPV (2) DPT (2) HB (2)

At 6 months of age OPV (3) DPT (3) HB (3)

At 9 months of age OPV (4)

At 12 months of age OPV (5) MMR

At 18 months of age OPV (booster) DPT (booster) MMR (booster)

Safe Handling of Vaccines

The numerous vaccines and other immunologic substances used by the practitioner vary in the storage temperatures required. Product package inserts should be consulted for detailed information on vaccine storage conditions and shelf life.

Safety of Immunization Although no vaccine is 100% safe and effective, vaccines have proven to be among the safest

of medical interventions. All vaccines have certain contraindications and precautions that guide their administration.

a) Healthy Children‒ Minor acute illnesses, with or without low-grade fever, are not contraindications to

vaccination, because there is no evidence that vaccination under these conditions increases the rate of adverse effects or decreases efficacy.

‒ A moderate to severe febrile illness may be a reason to postpone vaccination. ‒ Routine physical examination and temperature assessment are not necessary before

vaccinating healthy infants and children.b) Children with Chronic Illnesses

‒ Most chronic diseases are not contraindications to vaccination; in fact, children with

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chronic diseases may be at greater risk of complications from vaccine-preventable diseases, such as influenzal and pneumococcal infections.

‒ Premature infants are a good example. They should be immunized according to their chronologic, not gestational, age. Vaccine doses should not be reduced for preterm or low-birth-weight infants.

‒ One exception to this rule is children with progressive central nervous system disorders. Vaccination with DTaP should be deferred until the child's neurologic status has been clarified and is stable.

c) Immunodeficient Children‒ Congenitally immunodeficient children should NOT be immunized with live-virus

vaccines (oral polio vaccine [OPV], MMR, VAR, MMRV, yellow fever, or live-attenuated influenza vaccine [LAIV]) or live-bacteria vaccines (BCG or live typhoid fever vaccine).

‒ Children with cancer and children receiving high-dose corticosteroids or other immunosuppressive agents should not be vaccinated with live-virus or live-bacteria vaccines. This contraindication does not apply if the malignancy is in remission and chemotherapy has not been administered for at least 90 days.

‒ Live-virus vaccines may also be administered to previously healthy children receiving low to moderate doses of corticosteroids (defined as up to 2 mg/kg/d of prednisone or prednisone equivalent, with a 20 mg/d maximum) for less than 14 days; children receiving short-acting alternate-day corticosteroids; children being maintained on physiologic corticosteroid therapy without other immunodeficiency; and children receiving only topical, inhaled, or intraarticular corticosteroids.

‒ Contraindication of live-pathogen vaccines also applies to children with human immunodeficiency virus (HIV) infection who are severely immunosuppressed.

d) Allergic or Hypersensitive Children‒ Hypersensitivity reactions are rare following vaccination. They are generally attributable

to a trace component of the vaccine other than to the antigen itself; for example, MMR, IPV, and VAR contain microgram quantities of neomycin, and IPV also contains trace amounts of streptomycin and polymyxin B.

‒ Children with known anaphylactic responses to these antibiotics should not be given these vaccines.

‒ Trace quantities of egg antigens may be present in both inactivated and live influenza and yellow fever vaccines. Children who have had anaphylactic reactions to eggs should not be given these vaccines; children with less serious reactions to eggs can generally be safely immunized.

‒ Some vaccines (MMR, MMRV, and VAR) contain gelatin, a substance to which persons with known food allergy may develop an anaphylactic reaction. ------------------------------------------------------------------------------------------------------------

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